The aims of this proposal are to study aspects of cholesterol solubility in biocolloidal systems under the following general headings: 1. Metastability and micronucleation kinetics of cholesterol precipitation (for instance, in bile analog then natural systems) by the technique of quasielastic laser light scattering and sequential nephelometry (turbidimetry) as complementary approaches and concerning which our work has now shown feasibility. 2. Cholesterol metabolism within the limited domain related to our project in the prairie dog, a new and promising (from the standpoint of human relevance) animal model. One primary objective here is to develop a sufficient base of information, so as to make the model a useful surrogate for human testing of oral biochemical agents to dissolve gallstones, and otherwise favorably affect the distribution and inhibit precipitation of cholesterol in tissues and body fluids. 3. Development of an orally useful biotransformation-resistant phospholipid analog. The rationale is that this represents a highly original, serious and fundamental therapeutic approach to maintenance of metastability (#1). This work will require synthesis of well-designed radiolabeled compounds and testing for intestinal absorption, metabolic fate, pool distribution and solubility effects with precise techniques, including the use of high pressure liquid chromatography (HPLC) to achieve improved separation and quantitation in measurements of phospholipids and their analogs. 4. Energetics of phenomena related to all three of the foregoing projects, i.e., kinetic energy barriers to phase transitions during cholesterol micronucleation, various types of 'associative phenomena', purity assessment of phospholipids and analogs and possibly measurement of the reaction enthalpies of cholesterol metabolism regulating hepatic microsomal enzymes of differential scanning calorimetry.